Naturally occurring chlorophyll derivatives inhibit aflatoxin B 1-DNA adduct formation in hepatoma cells

Abstract

The inhibitory effects of four chlorophyll derivatives (chlorophyllide [Chlide] a and b and pheophorbide [Pho] a and b) on aflatoxin B 1 (AFB 1)-DNA adduct formation, and on the modulation of hepatic glutathione S-transferase (GST) were evaluated in murine hepatoma (Hepa-1) cells. Enzyme-linked immunosorbent assay showed that pretreatment with Chlide or Pho significantly reduced the formation of AFB 1-DNA adducts, and that Pho was the most potent inhibitor. However, wash-out prior to adding AFB 1 totally eliminated inhibition by Childe and partially eliminated inhibition by Pho, indicating that the inhibitory effect of Chlide, and to some extent Pho, was mediated through direct trapping of AFB 1. Furthermore, spectrophotometric analysis showed that Pho treatment could increase GST activity in Hepa-1 cells. These observations indicate that the chlorophyll derivatives studied may attenuate AFB 1-induced DNA damage in the Hepa-1 cell by direct trapping of AFB 1. Pho provided additional protection not only by direct trapping, but also by increasing GST activity against hepatic AFB 1 metabolites.